The concomitant use of vancomycin and piperacillin-tazobactam is associated with acute kidney injury (AKI) in extremely low birth weight infants (ELBW).

BACKGROUND: Late-onset sepsis is common in extremely low birth weight (ELBW) infants, and it leads to the use of antibiotics to cover resistant organisms, which can be nephrotoxic. Here we have investigated the role of vancomycin plus piperacillin-tazobactam on the rate of acute kidney injury (AKI). METHODS: In a retrospective case-control study, medical records of all ELBW infants who were admitted to our Neonatal Intensive Care Unit (NICU) with late onset sepsis who were prescribed vancomycin plus piperacillin-tazobactam were reviewed for demographics, clinical characteristics, use of potential nephrotoxic medications and outcomes. RESULTS: During the study period, 264 patients were admitted, of whom 28.4%(75/264) received vancomycin plus piperacillin-tazobactam and were matched with 64 controls. There were no differences in gestational age or birth weight between cases and controls [688±160 vs. 689±162 grams (p = 0.99), and 24.7±1.8 vs. 24.7±1.6 weeks (p = 0.99) respectively]. There was no difference in the rate of sepsis between cases and controls [76%(55/72) vs. 64%(41/64) respectively, p = 0.11]. Infants exposed to vancomycin plus piperacillin-tazobactam had a higher percentage of concomitant use of vasopressors and amphotericin. To adjust for confounders, a logistic regression analysis was conducted with AKI as the dependent variable. Use of vasopressors and vancomycin plus piperacillin-tazobactam were the only risk factors associated with AKI with an adjusted OR (95%CI) of 4.08 (1.90-8.74), p < 0.001; and 2.87 (1.26-6.53), p = 0.01 respectively. CONCLUSION: The use of vancomycin plus piperacillin-tazobactam in ELBW infants is associated with an increased risk for AKI.

Maternal risk factors associated with inadequate testing and loss to follow-up in infants with perinatal hepatitis C virus exposure.

OBJECTIVES: Inadequate testing (IT) and follow-up in infants with perinatal hepatitis C virus (HCV) exposure are challenging. We sought to identify maternal clinical and demographic risk factors that are associated with inadequate testing (IT) and follow-up of perinatally HCV-exposed infants. METHODS: In a retrospective cohort study spanning a period of 23 years, medical records of HCV-infected women and their perinatally exposed infants were reviewed for maternal characteristics that could be associated with their infants' IT and loss to follow-up. RESULTS: A total of 27% (108/407) of HCV-exposed infants were adequately tested (AT) for HCV perinatal transmission. Among AT infants, HCV transmission rate was 11% (12/108). History of maternal intravenous drug use (IVDU) was significantly higher in IT vs. AT infants [88% (193/218) vs. 76% (70/92); p = 0.005]. The percentage of mothers on methadone maintenance treatment during pregnancy was higher in AT vs. IT infants [53% (35/66) vs. 34% (65/186); p = 0.010]. The percentage of mothers with HCV medical care was higher among AT than IT infants [54% (56/102) vs. 41% (106/255); p = 0.022]. CONCLUSIONS: Infants born to HCV-infected mothers have suboptimal testing, possibly leading to an underestimation of the rate of HCV vertical transmission. Infants of mothers receiving HCV medical care and methadone treatment have improved testing. Infants of HCV-positive mothers with history of IVDU have lower rates of testing. Screening HCV-infected pregnant women for history of IVDU and linking them to drug treatment programs, and HCV medical care may improve testing and follow-up in their infants.

Low caloric intake and high fluid intake during the first week of life are associated with the severity of bronchopulmonary dysplasia in extremely low birth weight infants.

OBJECTIVE: To study whether there is an association between nutritional intake during the first week of life and severity of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. METHODS: In a retrospective cohort study, medical records of all ELBW infants admitted to our Neonatal Intensive Care Unit (2010-2017) were reviewed for infants' demographics, clinical characteristics, nutritional intake during their first week of life, and BPD risk factors. RESULTS: During the study period 226 infants were identified of whom 67% (151/226) had moderate-severe BPD and the rest served as controls. Overall infants with moderate-severe BPD were younger, smaller, and spent more time on mechanical ventilation than their controls [(mean±standard deviation) 24.7±1.7 vs. 26.8±2.0 weeks gestational age (p < 0.001); 678±154 vs. 837±129 grams (p < 0.001); and 37.9±23.6 vs. 13.7±15.3 days (p < 0.001) respectively]. During the first week of life, the average caloric, carbohydrate, protein and lipid intakes were significantly lower, and the average fluid intake was significantly higher in the moderate-severe BPD than the control group. After adjustment for confounders, fluid intake, and days on mechanical ventilation were significantly associated with moderate-severe BPD with an odds ratio [OR (95% confidence interval)] of 1.03 (1.01-1.04), and 1.05 (1.03-1.07) respectively. Daily caloric intake was associated with an increased risk for moderate-severe BPD [OR: 0.94 (0.91-0.97)]. CONCLUSION: Low caloric intake, and high fluid intake during the first week of life are associated with the severity of BPD in ELBW infants.

Enteral fish oil supplementation in the resolution of parenteral nutrition associated cholestasis.

OBJECTIVE: To analyze safety, tolerance and efficacy of enteral omega-3 fatty acids (FAs) in the resolution of Parenteral Nutrition Associated Cholestasis (PNAC) and postnatal growth among preterm neonates. STUDY DESIGN: This is a single center retrospective case-control study of all neonates born less than 32 weeks of gestation and developed PNAC (Direct bilirubin >2 mg/dl). Infants who received enteral omega-3 FAs supplementation (1 g/Kg/d) served as cases and were compared with gestational age, gender and direct bilirubin level matched controls who did not receive enteral omega-3 FAs supplementation. RESULTS: A total of 48 infants were analyzed, 24 who received enteral omega-3 fatty acids were matched with 24 controls. The omega-3 FAs and control groups were similar in gestational age (weeks) and birth weight (gram). Overall there were no differences between the two groups in infants' demographics or clinical characteristics including risk factors for the development of PNAC. Infants who received enteral omega-3 FAs had significantly fewer days of cholestasis (p = 0.025) and a higher average daily weight gain (grams/day) (p = 0.011) than their controls. In a linear regression analysis with days of cholestasis as the dependent variable and Ursodeoxycholic acid (UDCA) and Omega-3 FAs as independent variables, enteral omega-3 FAs remained associated with a shorter duration of cholestasis, p < 0.001. CONCLUSION: Enteral fish oil is inexpensive, safe & well tolerated in preterm neonates with no contraindications to enteral feeding. Enteral omega-3 FAs are easy to administer and help in rapid resolution of PNAC while promoting postnatal weight gain in preterm infants.

Effect of fluctuation of oxygenation and time spent in the target range on retinopathy of prematurity in extremely low birth weight infants.

BACKGROUND: The association between saturation of peripheral oxygenation (SpO2) fluctuation and severity of retinopathy of prematurity (ROP) is well elucidated in extremely low birth weight (ELBW) infants. Time spent in the Target range of SpO2 is also associated with the severity of ROP. METHODS: In a prospective observational study, the SpO2 of all ELBW infants admitted to our unit were monitored for the first four weeks of life, and averaged every minute for analysis. The percent time spent at SpO2 <90%, 90-95%, and >95% and weekly SpO2 fluctuations [as SpO2 coefficient of variation (CoV)] were calculated. RESULTS: During the study period 21 infants had moderate to severe ROP and 35 infants served as controls. Infants with moderate to severe ROP were smaller and younger than their controls [676±124 grams vs. 796±148 grams (p < 0.001); and 24.0±1.0 weeks vs. 25.0±1.7 weeks (p < 0.001) respectively]. There were no significant differences in time spent in the 90-95% range between groups (p = 0.66). However there was a significant increase in weekly SpO2 CoV in infants with moderate to severe ROP vs. controls (p = 0.007). CONCLUSION: In ELBW infants, there was an association between SpO2 fluctuation during the first four weeks of life and severity of ROP, although, no association was established with time spent in the target range of SpO2.

Weight gain and hypertension at three years of age and older in extremely low birth weight infants.

OBJECTIVE: To determine the prevalence and weight gain as a risk factor of hypertension (HTN) at three years of age and older among extremely low birth weight (ELBW) infants. STUDY DESIGN: Retrospective cohort study of all ELBW infants born and followed up at our institution over 15 years. RESULTS: 204 infants were followed up for [median (inter-quartile range)] 10.2 years (6.9-13.0). Their birth weight and gestational age were (mean±standard deviation) 758±149 g and 26.4±2.1 weeks respectively. At 3 years of age and older, the prevalence of HTN was 7.3% (15/204), and the prevalence of obesity was 13.2% (27/204). Obesity was more prevalent in children with than without HTN [33% (5/15) vs. 12% (22/189); p = 0.01]. In a regression analysis, body mass index (BMI) percentile at 3 years of age and older (p = 0.04) and increase in weight Z scores since birth (p = 0.008) were associated with a higher systolic blood pressure (SBP; R = 0.386, p <  0.001). CONCLUSION: Obesity is prevalent in ELBW infants at three years of age and older, and it is significantly associated with hypertension. An increase in BMI percentile at ≥3 years of age, and the rate of weight gain since birth among ELBW infants are associated with an increase in SBP.

Hepatitis C Virus universal screening versus risk based selective screening during pregnancy.

OBJECTIVES: We sought to compare the value of HCV universal screening versus risk-based selective screening in pregnant women. STUDY DESIGN: In a prospective observational study (Jan 2012 - March 2012), pregnant women, in a high risk inner city clinic, who were at "low risk" for HCV infection were tested for HCV antibodies (universal screening) and their medical records were compared to the medical records of pregnant women who were at "high risk" (risk based selective screening as assessed by their obstetricians' screening questionnaire). RESULTS: During the study period, 419 women delivered at our institution with 8.8% (37/419) at high risk for HCV. In 95% (183/193) of available and consenting low risk women, HCV antibody testing was done. The prevalence of HCV was 3.18% (7/220; 95% CI: 1.36-6.50) in all tested women versus 0.95% (4/419; 95% CI: 0.31-2.59) in risk-based selectively tested women. Overall the screening questionnaire had a sensitivity of 0.85 (0.42-0.99) and a specificity of 0.52 (0.45-0.58) in all women who had HCV antibody testing and questionnaire screening. CONCLUSIONS: Using a screening questionnaire to identify women at risk for HCV infection during pregnancy under-estimates the real prevalence of HCV. A universal screening should be considered in high risk cities.

Serum creatinine in very low birth weight infants during their first days of life.

OBJECTIVES: Little is known about the relationship between gestational age (GA) or birth weight (BW) and serum creatinine (SCr) in very low birth weight (VLBW) infants. We sought to study postnatal SCr changes and determine if there is a correlation between GA or BW and SCr in VLBW infants, during their first days of life. STUDY DESIGN: Medical records of all VLBW infants, who were admitted to our neonatal intensive care unit (NICU) between 1 May 1998 and 1 May 2001, were reviewed. Medical records were reviewed for: BW, GA, gender, race, APGAR scores, mechanical ventilation, use of medications, fluid intake, urinary output, protein intake, blood urea nitrogen (BUN) and SCr during the first days of life. Patients with anuria/oliguria, major congenital anomalies, low APGAR scores at 5 min, on high ventilator settings (on the oscillator), hemodynamically unstable (on pressors, inotropes) and on indomethacin and diuretics were excluded. RESULTS: In total, 138 infants met our inclusion criteria. SCr was found to decrease postnatally, reaching a plateau on day 5 of life in all VLBW infants (repeated measure analysis of variance; P=0.004); however, there was a delay in the decrease of SCr in the subgroup of infants <29 weeks GA, and <1000 g BW. SCr (on day 5 of life) was also found to decrease with increasing GA and BW (Pearson correlation coefficient: -0.206 (P=0.05) and -0.236 (P=0.05) respectively). CONCLUSION: In VLBW infants SCr decreases significantly during the first days of life; however, in infants younger than 29 weeks GA or smaller than 1000 g BW there is a delay in the decrease of their SCr that extends beyond the first days of life. We also conclude that during the first days of life, and in VLBW infants SCr decreases with advancing GA and BW.

Airway pressure release ventilation with a short release time in a child with acute respiratory distress syndrome.

Airway pressure release ventilation (APRV) allows ventilation and oxygenation to occur at lower peak and mean airway pressures than conventional positive pressure ventilation. The use of APRV in adults is an effective method of ventilation for patients with acute lung injury and acute respiratory distress syndrome. However, the use of APRV in children is less established. We report the use of APRV with a short release time of 0.2 s in a child with acute respiratory distress syndrome secondary to respiratory syncytial virus pneumonia.

Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice.

The pulmonary disease of cystic fibrosis (CF) is characterized by persistent airway obstruction, which has been attributed to chronic endobronchial infection and inflammation. The levels of exhaled nitric oxide (NO) are reduced in CF patients, which could contribute to bronchial obstruction through dysregulated constriction of airway smooth muscle. Because airway epithelium from CF mice has been shown to have reduced expression of inducible NO synthase, we examined airway responsiveness and relaxation in isolated tracheas of CF mice. Airway relaxation as measured by percent relaxation of precontracted tracheal segments to electrical field stimulation (EFS) and substance P, a nonadrenergic, noncholinergic substance, was significantly impaired in CF mice. The airway relaxation in response to prostaglandin E2 was similar in CF and non-CF animals. Treatment with the NO synthase inhibitor NG-nitro-L-arginine methylester reduced tracheal relaxation induced by EFS in wild-type animals but had virtually no effect in the CF mice. Conversely, exogenous NO and L-arginine, a NO substrate, reversed the relaxation defect in CF airway. We conclude that the relative absence of NO compromises airways relaxation in CF, and may contribute to the bronchial obstruction seen in the disease.

Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development.

Release of substance P (SP) from sensory nerve endings of the tracheobronchial system modulates airway smooth muscle contraction and may cause relaxation of precontracted airways. We sought to elucidate the effect of postnatal maturation on SP-induced relaxation of precontracted airways and determine the roles of endogenously generated nitric oxide (NO) and prostaglandins (PGs). Cylindrical airway segments were isolated from the midtrachea of rats at four different ages, 1, 2, and 4 wk and 3 mo, and contracted to 50-75% of the maximum response induced by bethanechol. SP was then administered in the absence and presence of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the PG inhibitor indomethacin, or both. Relaxation of airways with SP decreased significantly with advancing postnatal age. SP-induced tracheal relaxation was consistently attenuated by pretreatment with L-NAME, indomethacin, or both. In a different group of animals, L-NAME significantly attenuated the relaxant response of airways to PGE2 exposure, but indomethacin had no significant effect on the relaxant response to exogenous NO. We conclude that SP induces a relaxant effect on precontracted airway smooth muscle, which decreases with advancing age and is mediated via SP-induced release of NO and/or PG.